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Molecular Diagnostics

A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma

British Journal of Cancer volume 126, pages 1196–1204 (2022)Cite this article

Subjects

Abstract

Background

The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC.

Methods

We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC.

Results

We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85).

Conclusions

We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.

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Fig. 1: Genome-wide discovery and validation of a novel 7-miRNA panel to detect patients with ICC at high risk for short-term survival.
Fig. 2: Training and validation of the panel for identifying survival outcomes in patients with ICC.
Fig. 3: Validation of the panel in clinical plasma samples and the establishment of a final risk-stratification model for patients with ICC.

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Data availability

TCGA miRNA expression profiling data were downloaded from the University of California, Santa Cruz Xena Browser (https://xenabrowser.net). Normalised non-coding RNA profiling and clinical data from the GSE53870 dataset were downloaded from the Gene Expression Omnibus database.

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Acknowledgements

We thank Drs. Tatsuhiko Kakisaka, Satoshi Nishiwada, Geeta Sharma, Divya Sahu, In-Seob Lee, and Yasuyuki Okada for discussing the experiments and analysis. We thank Drs. Kensuke Yamamura, Takeo Toshima, Masaaki Nishi, Shinichiro Yamada, and Kazunori Tokuda, as well as Ms. Yumi Horikawa, for collecting clinical samples and information. We also would like to extend our thanks to Dr. Kerin Higa for her significant editing and useful suggestions for improving the quality of our manuscript.

Funding

This work was supported by CA72851, CA181572, CA184792, CA202797, and CA227602 grants from the National Cancer Institute, National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Yuma Wada & Ajay Goel

  2. Department of Surgery, Tokushima University, Tokushima, Japan

    Yuma Wada, Mitsuo Shimada, Yuji Morine, Tetsuya Ikemoto & Yu Saito

  3. Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA

    Yuma Wada & Ajay Goel

  4. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Hideo Baba

  5. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Mori

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Contributions

Y Wada: Study concept and design; specimen provider; acquisition of clinical data; analysis and interpretation of data and statistical analysis; drafting of the manuscript. M Shimada: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. Y Morine: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. T Ikemoto: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. Y Saito: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. H Baba: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. M Mori: Study concept and design; specimen provider; acquisition of clinical data; drafting of the manuscript. A Goel: Study concept and design; analysis and interpretation of data and statistical analysis; drafting of the manuscript

Corresponding author

Correspondence to Ajay Goel.

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The study was conducted in accordance with the Declaration of Helsinki. A written informed consent was obtained from all patients, and the study was approved by the institutional review boards of all participating institutions.

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No individual person’s data were used in this paper, and thus no consent for publication was required for these studies.

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The authors declare no competing interests.

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Wada, Y., Shimada, M., Morine, Y. et al. A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma. Br J Cancer 126, 1196–1204 (2022). https://doi.org/10.1038/s41416-022-01710-z

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